Transfer RNA

Transfer RNAs (tRNAs) have two functions that link the RNA and protein information systems. First, they must accept a specific amino acid, one of 20. They do this with accuracy greater than 99.99 percent, even distinguishing between chemically similar structures. But tRNAs share functions as well. The translating ribosome must be able to insert any of the 20 amino acids at the correct position in the growing polypeptide chain, with roughly the same efficiency. Otherwise, the number of proteins that a cell could make would be severely limited. This means that all tRNAs must have common structural features that are recognized by the ribosome.

You can see the common structural features of tRNAs at both the secondary and tertiary levels. Only a few sequences or bases are common to all tRNAs. The common secondary structure of tRNAs is the cloverleaf pattern, where the 5′ and 3′ sequences are base‐paired, and then the other three stem‐loops of the cloverleaf are formed by intramolecular base pairs over a short distance. All tRNAs end in the acceptor sequence, CCA, which furnishes a common structure for the ribosome to recognize. The CCA sequence is made either by transcription of the DNA template or added post‐transcriptionally by an enzyme. The A of the acceptor CCA sequence does not have a 2′ or 3′ phosphate. Depending on the exact tRNA species, the amino acid is loaded onto either the 2′ or 3′ hydroxyl group of the acceptor A in an ester linkage. The other part of the tRNA is the anticodon, which forms base pairs with the trinucleotide codon sequence of the ribosome‐bound message. The anticodon is found at the same place in each tRNA cloverleaf, away from the acceptor stem. This dual nature of tRNA provides a clue to its translation function: The acceptor stem accepts a specific amino acid, while the anticodon determines the placement of that amino acid at the correct point in the growing polypeptide chain.

The tertiary structure of all tRNAs are likewise similar. All known tRNAs are roughly L‐shaped, with the anticodon on one end of the L and the acceptor stem on the other. Each stem of the L is made up of two of the stems of the cloverleaf, arranged so that the base pairs of each stem are stacked on top of each other. The parts of the molecule that are not base‐paired are involved in other types of interactions, termed tertiary interactions. The tertiary structures of tRNAs thus reflect the dual functions of the molecule: The anticodons are well‐separated from the acceptor stems. This feature allows two tRNA molecules to interact with two codons that are adjacent on an mRNA molecule. See Figure 1.